Funds are requested for acquisition of a 2-channel transcranial magnetic stimulator (TMS) with simultaneous 60-channel electroencephalography (EEG) and 6-channel electromyogram (EMG) recording capability to the MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging. The fully integrated instrument system includes an advanced frameless stereotactic navigator that allows instantaneous calculation of the stimulated brain location and the direction and strength of the induced neural currents based on the individual subject's magnetic resonance image (MRI). The proposed TMS system allows non-invasive and safe inhibition or excitation of specific cortical areas, essentially switching the stimulated brain areas ON or OFF for a short time (~tens of milliseconds), thus enhancing or interrupting ongoing processing in the targeted brain areas. This powerful technology is the only method to allow non-invasive validation of models of human brain functions based on neuroimaging (fMRI/MEG/EEG/PET) data. Accurate navigation is needed to target the specific brain areas previously shown to be active with neuroimaging tools. Two TMS channels are needed to stimulate two different brain locations with a TMS pulse simultaneously or in rapid succession. This is necessary because even simple stimuli and tasks activate an anatomically dispersed network with nodes in widely separate parts of the brain, and in order to probe network properties and parallel processing in the human brain, TMS of one area is often not sufficient to significantly modulate brain function and/or behavioral indices. The simultaneous EEG allows direct on-line monitoring of how brain functions are modulated as a result of TMS and estimating functional connectivity across brain areas, offering a unique window into actually understanding causal connections between different brain areas and establishing causality between brain functions and perception/cognition/behavior. This robust combination of features thus allows full-scale reverse engineering of the human brain. This instrument will therefore benefit all ongoing studies of human brain functional organization. Further, some of our human studies focusing on haemodynamics- electrophysiology coupling should expect roughly 500-fold signal-to-noise increases by using navigated TMS instead of peripheral sensory stimulation for brain activation. Finally, our stroke and migraine studies will utilize simultaneous TMS+EEG to estimate cortical viability and excitability. The Nexstim eXimia navigator and EEG systems, along with two Medtronic MagPro X100 MagOption stimulators and Medtronic coils, were selected because of the individual state-of-the art components were found to be best suited to serve our wide user base. The eXimia EEG is also the only commercially available TMS- compatible EEG system, and no other combination offers navigation and simultaneous TMS and EEG/EMG in a seamless fully integrated instrument system. [unreadable] [unreadable] The navigated TMS+EEG instrument will be regularly employed by a large number of NIH funded projects, each of which is relevant to public health by helping to understand how the human brain works in health and disease. Validation of models (that are typically driven by imaging data) is a key element in any scientific reasoning; yet, in neuroscience, this has mainly relied on animal models or human stroke/lesion studies. This instrument allows safe and noninvasive reverse engineering of human brain functional organization and will thus have a strong impact on the validation of cognitive neuroscience models, while it will also increase our understanding of the haemodynamics-electrophysiology link as well as stroke and migraine pathophysiology. [unreadable] [unreadable] [unreadable]